Malaria is an acute and often chronic infectious disease resulting from the presence of protozoan parasites within red blood cells. Caused by single-celled parasites of the genus Plasmodium, malaria is transmitted from person to person by the bite of female mosquitoes.
The discovery of artemisinin (qinghaosu), a naturally occurring endoperoxide sesquiterpene lactone, triggered substantial efforts to elucidate its molecular mechanism of action and to identify novel antimalarial peroxides (Dong and Vennerstrom, Expert Opin. Ther. Patents 11, 1753-1760, (2001)). Many synthetic 1,2,4-trioxanes, 1,2,4,5-tetraoxanes, and other endoperoxides have been prepared.
A synthetic procedure for preparing compounds of Formula I, salts of the free base cis-adamantane-2-spiro-3′-8′-[[[(2′-amino-2′-methylpropyl)amino]carbonyl]methyl]-1′,2′,4′-trioxaspiro[4.5]decane has been disclosed in U.S. Pat. No. 6,906,205. WO 2007138435 also discloses a synthetic procedure for preparing compounds of Formula I. The free base obtained by this procedure involves the formation of dimer impurity, which affects the purity of the free base.
Therefore, there is a need to develop a process which provides the free base of high purity.